Chronic alcohol administration alters metabolomic profile of murine bone marrow.

Introduction: People with hazardous alcohol use are more susceptible to viral, bacterial, and fungal infections due to the effect of alcohol on immune system cell function. Metabolized ethanol reduces NAD+ to NADH, affecting critical metabolic pathways. Here, our aim was to investigate whether alcohol is metabolized by bone marrow cells and if it impacts the metabolic pathways of leukocyte progenitor cells. This is said to lead to a qualitative and quantitative alteration of key metabolites which may be related to the immune response. Methods: We addressed this aim by using C57BL/6 mice under chronic ethanol administration and evaluating the metabolomic profile of bone marrow total cells by gas chromatography-coupled mass spectrometry (GC-MS). Results: We identified 19 metabolites. Our data demonstrated that chronic ethanol administration alters the metabolomic profile in the bone marrow, resulting in a statistically diminished abundance of five metabolites in ethanol-treated animals: uracil, succinate, proline, nicotinamide, and tyrosine. Discussion: Our results demonstrate for the first time in the literature the effects of alcohol consumption on the metabolome content of hematopoietic tissue and open a wide range of further studies to investigate mechanisms by which alcohol compromises the cellular function of the immune system.

DNA methylation profile of genes related to immune response in generalized periodontitis.

BACKGROUND AND OBJECTIVE: Epigenetic events, as the DNA methylation, may be related to development of inflammatory diseases. Due to the important role of host's response in the pathogenesis of periodontitis, the purpose of the present study was to investigate the methylation profile of genes related to immune response in gingival tissues from patients with generalized periodontitis (GP) compared to healthy individuals. METHODS: Gingival tissues were collected from 20 individuals with GP and 20 healthy individuals. Genomic DNA was extracted and submitted to enzymatic digestions. An initial screening using a panel of genes involved with the response immune was performed in pools containing six samples of each group. Genes that presented different levels of methylation between the groups were selected for individual assays for validation. RESULTS: The array results showed an unmethylated profile in the majority of genes evaluated in both groups. MALT1, LTB, and STAT5 genes presented a profile of partial methylation in the control compared with GP group. Validation individual assays using a larger number of samples (n = 20, each group) confirmed the hypomethylation of STAT5 in the GP group compared with control group (P < .001). CONCLUSION: Generalized periodontitis is associated with hypomethylation of the STAT5 gene. Further studies are necessary to evaluate the functional impact these findings.

Loss of heterozygosity of MIR15A/MIR16-1, negative regulators of the antiapoptotic gene BCL2, is not common in odontogenic keratocysts.

OBJECTIVES: The odontogenic keratocyst (OKC) is an aggressive odontogenic cyst that has a high recurrence rate. Apart from PTCH1 mutations, few molecular alterations are described in OKCs. Low expression of microRNAs (miRNAs) miR-15a and/or miR-16-1 in association with increased expression of their target, Bcl-2, have been previously found in OKC. In humans, MIR15A and MIR16-1 are clustered at chromosome position 13 q14, and loss of heterozygosity (LOH) at this locus occurs in different tumors. We aimed to determine whether deletion at 13 q14 is a potential mechanism leading to miR-15a/16-1 aberrant expression in OKC. METHODS: Genomic DNA was extracted from 15 formalin-fixed, paraffin-embedded microdissected OKC cases. The polymorphic DNA markers D13S272 and D13S273 on chromosome 13 q14.3, around MIR15A/MIR16-1, were amplified by polymerase chain reaction. LOH was examined by capillary electrophoresis DNA-fragment analysis. RESULTS: The D13S272 marker had no LOH in 12 informative cases, whereas 2 out of 9 informative cases (22%) had LOH at the D13S273 marker. CONCLUSIONS: An LOH event at MIR15A/MIR16-1 locus is not common in OKC. The mechanism underlying the regulation of miR-15a and miR-16-1 expression in OKC remains to be determined.

DNMT3B (C46359T) polymorphisms and immunoexpression of DNMT3b and DNMT1 proteins in oral lichen planus.

OBJECTIVE: To investigate the DNMT3B (C46359T) polymorphism and immunoexpression of DNMT3b and DNMT1 in oral lichen planus (OLP) compared to a control group. METHODS: We aimed to investigate the DNMT3B (C46359T) polymorphism and immunoexpression of DNMT3b and DNMT1 in OLP (n = 32), comparing it with oral mucosa (control; n = 24). The DNMT3B (C46359T) polymorphism was analyzed using the RFLP-PCR and DNMT1, and DNMT3a proteins were identified using immunohistochemistry. We also compared the DNMT3B expression in OLP and oral inflammatory fibrous hyperplasia (OIFH), another oral inflammatory disease. Differences between the groups were determined by specific statistical analyses. RESULTS: The CT genotype of DNMT3B was associated with OLP development (p = 0.012). Increased expression of DNMT3B and DNMT1 was observed in OLP compared to the control group (p = 0.014 and p = 0.001, respectively). A significant increase in DNMT3B protein levels was observed in the genotype CT in DNMT3B (C46359T) polymorphisms (p = 0.045). No DNMT3B expression differences between OLP and OIFH were observed. CONCLUSIONS: Our data show that the DNMT3B (C46359T) polymorphism is associated with OLP development. Furthermore, increased expression of the enzyme DNMT3B, an epigenetic-associated protein, is present in OLP.

Carcinoma escamocelular bucal diagnosticado precozmente / Oral squamocellular carcinoma with early diagnosis

El carcinoma escamocelular es la neoplasia maligna más común en la cavidad bucal. Los sitios anatómicos más frecuentemente afectados son el labio inferior, los bordes laterales de lengua y el suelo de la boca. Su etiología es multifactorial, aunque está íntimamente relacionada con factores ambientales como el tabaquismo y el alcoholismo. El cuadro clínico se caracteriza generalmente por la presencia de placas blancas, placas eritematosas, placas entre eritematosas y blancas, úlceras de bordes levantados y masas exofíticas. El tratamiento consiste en la extirpación quirúrgica, la radioterapia, quimioterapia o ambos tratamientos. Este artículo presenta un caso de carcinoma escamocelular bucal en un paciente del sexo masculino, de 70 años de edad. En el mismo se describen los hallazgos clínicos, histopatológicos y el tratamiento correspondiente del caso. El diagnóstico precoz y correcto posibilitó la cura en este caso(AU)

The squamocellular carcinoma is a malignant neoplasm commonest in the buccal cavity. The more frequently involved anatomical sites are the lower lip, the tongue's lateral edges and the mouth floor. Its etiology is multifactor although it is closely related to smoking and alcoholism. Clinical picture is generally characterized by the presence of different types of white, erythematous, between erythematous and white plaques, ulcers with raised edges and exophytic masses. Treatment includes surgical removal, radiotherapy, chemotherapy or both. In present paper the case of a man aged 70 presenting with buccal squamous carcinoma describing the clinical, and the histopathologic findings and its corresponding treatment. The early and appropriate diagnosis allowed the cure of this case(AU)

Immunolocalization of DNMT1 and DNMT3a in salivary gland neoplasms.

OBJECTIVE: Salivary gland neoplasms pathogenesis has not been well established. DNA methylation occurs when methyl groups are added to cytosine nucleotides in specific areas of the gene by the enzyme DNA methyltransferase (DNMT). This chemical modification can alter gene expression without altering DNA sequence. While DNMT3a is mostly involved in de novo methylation, DNMT1 acts as a maintenance methyltransferase. We aimed to investigate the immunoexpression of DNMT3a and DNMT1 in minor salivary gland neoplasms, comparing it with normal tissue. MATERIAL: Forty-four formalin-fixed and paraffin-embedded samples of pleomorphic adenoma, adenoid cystic carcinoma, mucoepidermoid carcinoma and polymorphous low-grade adenocarcinoma were included in the study. The DNMT1 and DNMT3a proteins were identified by using a highly sensitive polymer-based system. RESULTS: Positive nuclear and cytoplasmic labeling for DNMT1 was observed in all samples, including the controls. Positive nuclear labeling for DNMT3a was found only in few neoplasms: 1 pleomorphic adenoma (9.0%), 2 adenoid cystic carcinoma (16.6%) and 1 mucoepidermoid (9.0%) cases. CONCLUSION: Our results were not able to demonstrate a clear correlation between DNMT1 and DNMT3a immunoexpression and salivary gland neoplasms development.